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https://www.readbyqxmd.com/read/29755323/environmental-enrichment-prevents-transcriptional-disturbances-induced-by-alpha-synuclein-overexpression
#1
Zinah Wassouf, Thomas Hentrich, Sebastian Samer, Carola Rotermund, Philipp J Kahle, Ingrid Ehrlich, Olaf Riess, Nicolas Casadei, Julia M Schulze-Hentrich
Onset and progression of neurodegenerative disorders, including synucleinopathies such as Parkinson's disease, have been associated with various environmental factors. A highly compelling association from a therapeutic point of view has been found between a physically active lifestyle and a significantly reduced risk for Parkinson's disease. Mimicking such conditions in animal models by promoting physical activity, social interactions, and novel surroundings yields in a so-called enriched environment known to enhance adult neurogenesis, increase synaptic plasticity, and decelerate neuronal loss...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29739797/epigenetic-regulation-of-aldosterone-synthase-gene-by-sodium-and-angiotensin-ii
#2
Yoshimichi Takeda, Masashi Demura, Fen Wang, Shigehiro Karashima, Takashi Yoneda, Mitsuhiro Kometani, Atsushi Hashimoto, Daisuke Aono, Shin-Ichi Horike, Makiko Meguro-Horike, Masakazu Yamagishi, Yoshiyu Takeda
BACKGROUND: DNA methylation is believed to be maintained in adult somatic cells. Recent findings, however, suggest that all methylation patterns are not stable. We demonstrate that stimulatory signals can change the DNA methylation status around transcription factor binding sites and a transcription start site and activate expression of the aldosterone synthase gene ( CYP11B2 ). METHODS AND RESULTS: DNA methylation of CYP11B2 was analyzed in aldosterone-producing adenomas, nonfunctioning adrenal adenomas, and adrenal glands and compared with the gene expression levels...
May 8, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29738496/endogenous-purification-of-nr4a2-nurr1-identified-poly-adp-ribose-polymerase-1-as-a-prime-coregulator-in-human-adrenocortical-h295r-cells
#3
Erika Noro, Atsushi Yokoyama, Makoto Kobayashi, Hiroki Shimada, Susumu Suzuki, Mari Hosokawa, Tomohiro Takehara, Rehana Parvin, Hiroki Shima, Kazuhiko Igarashi, Akira Sugawara
Aldosterone is synthesized in zona glomerulosa of adrenal cortex in response to angiotensin II. This stimulation transcriptionally induces expression of a series of steroidogenic genes such as HSD3B and CYP11B2 via NR4A (nuclear receptor subfamily 4 group A) nuclear receptors and ATF (activating transcription factor) family transcription factors. Nurr1 belongs to the NR4A family and is regarded as an orphan nuclear receptor. The physiological significance of Nurr1 in aldosterone production in adrenal cortex has been well studied...
May 8, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29695291/dna-topoisomerase-ii%C3%AE-stimulates-neurite-outgrowth-in-neural-differentiated-human-mesenchymal-stem-cells-through-regulation-of-rho-gtpases-rhoa-rock2-pathway-and-nurr1-expression
#4
Merve Zaim, Sevim Isik
BACKGROUND: DNA topoisomerase IIβ (topo IIβ) is known to regulate neural differentiation by inducing the neuronal genes responsible for critical neural differentiation events such as neurite outgrowth and axon guidance. However, the pathways of axon growth controlled by topo IIβ have not been clarified yet. Microarray results of our previous study have shown that topo IIβ silencing in neural differentiated primary human mesenchymal stem cells (hMSCs) significantly alters the expression pattern of genes involved in neural polarity, axonal growth, and guidance, including Rho-GTPases...
April 25, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29686604/ultrasound-triggered-effects-of-the-microbubbles-coupled-to-gdnf-plasmid-loaded-pegylated-liposomes-in-a-rat-model-of-parkinson-s-disease
#5
Peijian Yue, Wang Miao, Lin Gao, Xinyu Zhao, Junfang Teng
Background: The purpose of this study was to investigate ultrasound-triggered effects of PEGylated liposomes-coupled microbubbles mediated gene transfer of glial cell line-derived neurotrophic factor (GDNF) plasmid (PLs-GDNF-MBs) on behavioral deficits and neuron loss in a rat model of Parkinson's disease (PD). Methods: The unloaded PLs-MBs were characterized for particle size, concentration and zeta potential. PD rat model was established by a unilateral 6-hydroxydopamine (6-OHDA) lesion. Rotational, climbing pole, and suspension tests were used to evaluate behavioral deficits...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29626009/the-nurr1-ligand-1-1-bis-3-indolyl-1-p-chlorophenyl-methane-modulates-glial-reactivity-and-is-neuroprotective-in-mptp-induced-parkinsonism
#6
Sean L Hammond, Katriana A Popichak, Xi Li, Lindsay G Hunt, Evan H Richman, Pranav Damale, Edwin Chong, Donald S Backos, Stephen Safe, Ronald B Tjalkens
The orphan nuclear receptor, Nurr1 (NR4A2), regulates inflammatory gene expression in glial cells, as well as genes associated with homeostatic and trophic function in dopaminergic neurons. Despite these known functions of Nurr1, an endogenous ligand has not been discovered. We postulated that activation of Nurr1 would suppress activation of glia and thereby protect against loss of dopamine (DA) neurons following subacute lesioning with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Our previous studies have shown that a synthetic Nurr1 ligand, 1,1-bis(3'-indolyl)-1-(p-chlorophenyl)methane (C-DIM12), suppresses inflammatory gene expression in primary astrocytes and induces a dopaminergic phenotype in neurons...
April 6, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29576706/rhynchophylline-downregulates-phosphorylated-camp-response-element-binding-protein-nuclear-receptor-related-1-and-brain-derived-neurotrophic-factor-expression-in-the-hippocampus-of-ketamine-induced-conditioned-place-preference-rats
#7
Youli Guo, Chaohua Luo, Genghong Tu, Chan Li, Yi Liu, Wei Liu, Ken Kin Lam Yung, Zhixian Mo
Background: Addiction to ketamine is becoming a serious public health issues, for which there exists no effective treatment. Rhynchophylline (Rhy) is an alkaloid extracted from certain Uncaria species that is well known for both its potent anti-addictive and neuroprotective properties. Increasing evidence supports the contributions of cAMP response element binding protein (CREB), nuclear receptor-related-1 (Nurr1), and brain-derived neurotrophic factor (BDNF) in modulating neural and behavioral plasticity which was induced by addictive drugs...
January 2018: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29575325/neural-stem-cell-grafts-promote-astroglia-driven-neurorestoration-in-the-aged-parkinsonian-brain-via-wnt-%C3%AE-catenin-signalling
#8
Francesca L'Episcopo, Cataldo Tirolo, Luca Peruzzotti-Jametti, Maria F Serapide, Nunzio Testa, Salvatore Caniglia, Beatrice Balzarotti, Stefano Pluchino, Bianca Marchetti
During aging - one the most potent risk factors for Parkinson's disease (PD) - both astrocytes and microglia undergo functional changes that ultimately hamper homoeostasis, defence and repair of substantia nigra pars compacta (SNpc) midbrain dopaminergic (mDA) neurons. We tested the possibility of rejuvenating the host microenvironment and boosting SNpc DA neuronal plasticity via the unilateral transplantation of syngeneic neural stem/progenitor cells (NSCs) in the SNpc of aged mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced experimental PD...
March 25, 2018: Stem Cells
https://www.readbyqxmd.com/read/29565514/correlation-between-nurr1-expression-and-drug-resistance-in-the-brain-of-rats-with-epilepsy
#9
H-Y Li, F Liu, H-R Wang
OBJECTIVE: To investigate the correlation between nuclear receptor related 1 (Nurr1) expression and drug resistance in the brain of rats with epilepsy. MATERIALS AND METHODS: A total of 60 adult male Sprague-Dawley rats were selected, and the animal model of epilepsy was established by electrical stimulation. These rats were randomly divided into the control group and the drug-resistant group. The model of drug-resistant epilepsy was screened with phenytoin (PHT) and phenobarbital (PB); the hippocampus and temporal lobe cortex tissues were isolated from rats; the messenger ribonucleic acid (mRNA) and protein levels of Nurr1 in the hippocampus and cortex tissues of the two groups of rats were detected by reverse transcription polymerase chain reaction (RT-PCR), Western blotting and immunohistochemistry, respectively...
March 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29564810/kir6-2-deficiency-promotes-mesencephalic-neural-precursor-cell-differentiation-via-regulating-mir-133b-gdnf-in-a-parkinson-s-disease-mouse-model
#10
Yan Zhou, Jialei Zhu, Yang Lv, Chenghuan Song, Jianhua Ding, Ming Xiao, Ming Lu, Gang Hu
The loss of dopaminergic (DA) neurons in the substantia nigra (SN) is a major feature in the pathology of Parkinson's disease (PD). Using neural stem or progenitor cells (NSC/NPCs), the prospect of replacing the missing or damaged DA neurons is very attractive for PD therapy. However, little is known about the endogenous mechanisms and molecular pathways regulating the NSC/NPC proliferation and differentiation in the development of PD. Herein, using Kir6.2 knockout (Kir6.2-/- ) mice, we observed that genetic deficiency of Kir6...
March 21, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29540663/mir-381-3p-knockdown-improves-intestinal-epithelial-proliferation-and-barrier-function-after-intestinal-ischemia-reperfusion-injury-by-targeting-nurr1
#11
Liwei Liu, Jihong Yao, Zhenlu Li, Guo Zu, Dongcheng Feng, Yang Li, Wasim Qasim, Su Zhang, Tong Li, Huizhi Zeng, Xiaofeng Tian
Impairment in gut barrier function induced by intestinal ischemia/reperfusion (I/R) injury is associated with high morbidity and mortality. Intestinal barrier function requires the tight coordination of epithelial migration, proliferation and differentiation. We previously observed that nuclear receptor-related protein 1 (nurr1)-mediated proliferative pathway was impaired in intestinal I/R injury. Here, we aimed to assess the effect of nurr1 on intestinal barrier function and to evaluate microRNA (miRNA)-nurr1-mediated restoration of intestinal barrier function in intestinal I/R injury...
March 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29526736/mir-34b-c-regulates-wnt1-and-enhances-mesencephalic-dopaminergic-neuron-differentiation
#12
Roberto De Gregorio, Salvatore Pulcrano, Claudia De Sanctis, Floriana Volpicelli, Ezia Guatteo, Lars von Oerthel, Emanuele Claudio Latagliata, Roberta Esposito, Rosa Maria Piscitelli, Carla Perrone-Capano, Valerio Costa, Dario Greco, Stefano Puglisi-Allegra, Marten P Smidt, Umberto di Porzio, Massimiliano Caiazzo, Nicola Biagio Mercuri, Meng Li, Gian Carlo Bellenchi
The differentiation of dopaminergic neurons requires concerted action of morphogens and transcription factors acting in a precise and well-defined time window. Very little is known about the potential role of microRNA in these events. By performing a microRNA-mRNA paired microarray screening, we identified miR-34b/c among the most upregulated microRNAs during dopaminergic differentiation. Interestingly, miR-34b/c modulates Wnt1 expression, promotes cell cycle exit, and induces dopaminergic differentiation. When combined with transcription factors ASCL1 and NURR1, miR-34b/c doubled the yield of transdifferentiated fibroblasts into dopaminergic neurons...
April 10, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29481521/proliferation-and-committed-differentiation-into-dopamine-neurons-of-neural-stem-cells-induced-by-the-active-ingredients-of-radix-astragali
#13
Han Gao, Lianrong Dou, Liang Shan, Yan Sun, Wentao Li
Neural stem cells (NSCs) are important cellular sources of transplantation therapies for Parkinson's disease. This study aimed to determine the effects of extracts of radix astragali on the proliferation and differentiation into dopamine (DA) neurons in NSCs. NSCs were dealt with astragaloside IV (ASI), astragalus polysaccharide (APS), and astraisoflavan (ASF), the main active ingredients of radix astragali. First, the results from cell-count kit-8 (CCK-8) assay showed that ASI, ASF, and APS had positive effects on the proliferation of NSCs...
May 2, 2018: Neuroreport
https://www.readbyqxmd.com/read/29476799/effects-of-rhynchophylline-on-the-hippocampal-mirna-expression-profile-in-ketamine-addicted-rats
#14
Chan Li, Genghong Tu, Chaohua Luo, Youli Guo, Miao Fang, Chen Zhu, Hancheng Li, Jinying Ou, Yuting Zhou, Wei Liu, Ken Kin Lam Yung, Zhixian Mo
In the past few years, ketamine, a noncompetitive NMDA antagonist, has been widely abused worldwide as a new type of synthetic drug, severely affecting the physical and mental health of ketamine abusers. Previous studies have suggested that rhynchophylline can alleviate drug abuse and reverse the conditioned place preference caused by the abuse. MicroRNAs (miRNAs) are important factors regulating gene expression and are involved in the drug addiction process. The hippocampus is a critical area in the brain involved in causing drug addiction...
February 22, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29450981/nurr1-promotes-neurogenesis-of-dopaminergic-neuron-and-represses-inflammatory-factors-in-the-transwell-coculture-system-of-neural-stem-cells-and-microglia
#15
Xiaoxiang Chen, Yuan Qian, Xiangpeng Wang, Zhiwei Tang, Jiaotian Xu, Hai Lin, Zhiyong Yang, Xiaobin Song, Di Lu, Jiazhi Guo, Ligong Bian, Yu Li, Lei Zhou, Xingli Deng
INTRODUCTION: Neural stem cells (NSCs) are the most promising cells for cell replacement therapy for Parkinson's disease (PD). However, a majority of the transplanted NSCs differentiated into glial cells, thereby limiting the clinical application. Previous studies indicated that chronic neuroinflammation plays a vital role in the degeneration of midbrain DA (mDA) neurons, which suggested the developing potential of therapies for PD by targeting the inflammatory processes. Thus, Nurr1 (nuclear receptor-related factor 1), a transcription factor, has been referred to play a pivotal role in both the differentiation of dopaminergic neurons in embryonic stages and the maintenance of the dopaminergic phenotype throughout life...
February 15, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29429051/cilostazol-mediated-nurr1-and-autophagy-enhancement-neuroprotective-activity-in-rat-rotenone-pd-model
#16
Shireen A Hedya, Marwa M Safar, Ashraf K Bahgat
Nuclear receptor related 1 (Nurr1) orphan receptor has emerged as a promising contender in ameliorating Parkinson's disease; thus, finding a suitable activator of Nurr1 receptor is an attracting target for treating PD. Cilostazol, a phosphodiesterase-3 inhibitor, recently showed a favorable neuroprotective activity in multiple devastating central disorders, yet the possible antiparkinsonian activity of the drug has not been fully elucidated. Thus, the aim of this study is to explore the neuroprotective effect of cilostazol in rotenone-induced PD model in rats...
February 10, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29416637/liver-x-receptors-agonist-promotes-differentiation-of-rat-bone-marrow-derived-mesenchymal-stem-cells-into-dopaminergic-neuron-like-cells
#17
Oumei Cheng, Xiaoyan Tian, Ying Luo, Shaoshan Mai, Yang Yang, Shengnan Kuang, Qi Chen, Jie Ma, Beibei Chen, Rong Li, Lu Yang, Huan Li, Congli Hu, Jiahua Zhang, Zhihao Chen, Yuke Li, Hui Xia, Ying Xu, Junqing Yang
Dopaminergic (DA) neurons derived from bone marrow derived mesenchymal stem cells (BMSCs) maybe a valuable source for cell replacement therapy in Parkinson disease. Recent studies showed that new functions of LXR and their ligands have been proposed to prevent PD in the adult nervous system. The present study was designed to observe the effect of liver X receptors (LXR) agonist on differentiation of rat BMSCs into DA neurons. Expressions of the neuronal markers (Tuj1 and Nestin), the specific marker of DA neurons (tyrosine hydroxylase, TH), LXR α and LXR β were measured by immunocytochemical assay and TH/Tuj1 positive cells were determined by quantitative cell count analyses...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29404959/conserved-upstream-regulatory-regions-in-mammalian-tyrosine-hydroxylase
#18
Meng Wang, Lilah Fones, John W Cave
Tyrosine hydroxylase (Th) encodes the rate-limiting enzyme in catecholamine biosynthesis, and the regulation of its transcription is critical for the specification and maintenance of catecholaminergic neuron phenotypes. For many genes, regulatory genomic DNA sequences that are upstream of the proximal promoter control expression levels as well as region-specific expression patterns. The regulatory architecture of the genomic DNA upstream of the Th proximal promoter, however, is poorly understood. In this study, we examined the 11 kb upstream nucleotide sequence of Th from nine mammalian species and identified five highly conserved regions...
February 5, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29401702/bioactive-dietary-vdr-ligands-regulate-genes-encoding-biomarkers-of-skin-repair-that-are-associated-with-risk-for-psoriasis
#19
Amitis Karrys, Islam Rady, Roxane-Cherille N Chamcheu, Marya S Sabir, Sanchita Mallick, Jean Christopher Chamcheu, Peter W Jurutka, Mark R Haussler, G Kerr Whitfield
Treatment with 1,25-dihydroxyvitamin D₃ (1,25D) improves psoriasis symptoms, possibly by inducing the expression of late cornified envelope ( LCE )3 genes involved in skin repair. In psoriasis patients, the majority of whom harbor genomic deletion of LCE3B and LCE3C ( LCE3C_LCE3B-del ), we propose that certain dietary analogues of 1,25D activate the expression of residual LCE3A/LCE3D/LCE3E genes to compensate for the loss of LCE3B / LCE3C in the deletant genotype. Herein, human keratinocytes (HEKn) homozygous for LCE3C_LCE3B-del were treated with docosahexaenoic acid (DHA) and curcumin, two low-affinity, nutrient ligands for the vitamin D receptor (VDR)...
February 4, 2018: Nutrients
https://www.readbyqxmd.com/read/29291419/neuroprotective-effect-of-olfactory-ensheathing-cells-co-transfected-with-nurr1-and-ngn2-in-both-in-vitro-and-in-vivo-models-of-parkinson-s-disease
#20
Qingqing Liu, Qi Qin, Hongxue Sun, Di Zhong, Ran An, Yushuang Tian, Hongping Chen, Jing Jin, Haining Wang, Guozhong Li
AIMS: The aim of the study is to evaluate the neuroprotective effects of olfactory ensheathing cells (OECs) with the overexpression of nuclear receptor-related factor 1 (Nurr1) and neurogenin 2 (Ngn2) in experimental models of Parkinson's disease (PD) and to elucidate the potential mechanism underlying the neuroprotective effects of OECs-Nurr1-Ngn2. MATERIALS AND METHODS: In vitro study, OECs-Nurr1-Ngn2 conditioned medium (CM) was added to MPP+ -treated PC12 cells for 24h, and then the viability of PC12 cells, oxidative stress and apoptosis were detected...
February 1, 2018: Life Sciences
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